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NEUROPEPTIDE Y ASSOCIATES WITH GFR LOSS AND PROTEINURIA AND PREDICTS THE EVOLUTION OF CKD TOWARD KIDNEY FAILURE: A STUDY IN TWO EUROPEAN CKD COHORTS

INTRODUCTION AND AIMS: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with wide ranging effects in various organ systems, from the central nervous system to the cardiovascular system, the bone and the kidney . This neurotransmitter which has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases. NPY contributes to kidney damage in experimental models but the possibility that it is involved in CKD progression in humans has never been explored.

METHODS: We investigated the relationship between circulating NPY and the evolution of the GFR and proteinuria (by the Mixed Linear Model) and the risk for a combined end-point (>30% GFR loss, dialysis/transplantation or death, by Cox’s regression analysis) in two large European CKD cohorts including 753 (Italian cohort) and 576 (Dutch cohort) patients followed up for 36 and 57 months respectively.

RESULTS: In separate analyses of the two cohorts, NPY associated with the evolution of the eGFR and proteinuria over time both in unadjusted and adjusted analyses (P<0.001 for both biomarkers) . In a joint analysis of the two cohorts NPY predicted (P<0.001) the combined renal end point in a multivariate Cox’s model including baseline eGFR and 24h urinary protein and other potential confounders and the hazard ratio by NPY for the combined endpoint was similar and significant in the two cohorts [HR (25 pmol/L), first cohort: 1.12, 95% CI: 1.02-1.22, P=0.02; second cohort: 1.08, 95% CI: 1.01-1.16, P=0.048].

CONCLUSIONS: NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPY molecule, including interference with innate immunity and inflammation, may play a relevant role in CKD progression.